Regional contributions ofKv1.4,Kv4.2, andKv4.3to transient outward K⁺current in rat ventricle

Abstract

The aim of the present study was to assess differences in transient outward potassium current ( I to) between the right ventricular free wall and the interventricular septum of the adult rat ventricle and to evaluate the relative contributions of Kv4.2, Kv4.3, and Kv1.4 to I to in these regions. The results show that I to is composed of both rapidly and slowly recovering components in the right wall and septum. The fast component had a significantly higher density in the right free wall than in the septum, whereas the slow component did not differ between the two sites. Kv4.2mRNA and protein levels were also highest in the right wall and correlated with I to density, whereas Kv4.3 was expressed uniformly in these regions. The kinetics of the rapidly recovering component of I to in myocytes was similar to that recorded in tsa-201 cells expressing Kv4.2 and Kv4.3 channels. Kv1.4 mRNA and protein expression correlated well with the density of the slowly recovering I to, whereas the recovery kinetics of the slow component were identical to Kv1.4 expressed in tsa-201 cells. In conclusion, expression of Kv1.4, Kv4.2, and Kv4.3 differs between regions in rat hearts. Regionally specific differences in the genetic composition of I to can account for the region-specific properties of this current.

Myocardial infarction in rat eliminates regional heterogeneity of AP profiles,ItoK+currents, and [Ca2+]itransients

“…Unlike Kv4.2, Kv4.3 protein expression did not differ between the RVW and SEP myocytes and was not changed after MI. The regional differences in Kv4.2 and Kv4.3 channel expression are identical to that recently reported in normal rat heart (45,58).…”

“…Similar correlations between Kv4.x genes and I to have been documented in humans (17,28,52) and other animal species (16,17,21,25,58,59). By contrast, no regional differences in Kv4.3 expression were observed.…”

“…Rat hearts were quickly removed and retrogradely perfused with Tyrode solution for 20 s. Immediately after this procedure, the RVW and SEP were dissected (4 rats per group) and stored at Ϫ80°C before isolation of membrane proteins, as previously described (58). Total heart protein (50-100 g) and 10-20 g of total brain protein were resolved on a 10% sodium dodecyl sulfatepolyacrylamide gel electrophoresis and transferred to a polyvinylidene difluoride membrane.…”

“…This electrical heterogeneity in normal myocardium correlates with regional differences in the Ca 2ϩ -independent transient outward K ϩ current density (I to ) (5,15,18,34,35,43) as well as in gene expression of K ϩ channels (8,16,58). APD prolongation and reductions in I to density occur in rat heart after left anterior descending coronary artery ligation (2,43,58), aortic banding (5,22,55), as well as after treatment with either catecholamine (11) or monocrotaline (32,33). Depending on the model, the extent of I to density changes in disease may not be uniform throughout the ventricle (2,5,11,22,55), thereby leading to possible losses of electrical heterogeneity and increased susceptibility to arrhythmias (3).…”

“…right ventricle; septum; heart disease; contraction THERE ARE MARKED DIFFERENCES in the action potential duration (APD) in different regions of the mammalian ventricle (4,15,18,39,58). This electrical heterogeneity in normal myocardium correlates with regional differences in the Ca 2ϩ -independent transient outward K ϩ current density (I to ) (5,15,18,34,35,43) as well as in gene expression of K ϩ channels (8,16,58). APD prolongation and reductions in I to density occur in rat heart after left anterior descending coronary artery ligation (2, 43, 58), aortic banding (5, 22, 55), as well as after treatment with either catecholamine (11) or monocrotaline (32, 33).…”